Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: HNRNPL

Gene summary for HNRNPL

Gene summary.

Gene information	Species	Human
	Gene symbol	HNRNPL
	Gene ID	3191
	Gene name	heterogeneous nuclear ribonucleoprotein L
	Gene Alias	HNRPL
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	P14866

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
3191	HNRNPL	P107T-E	Human	Esophagus	ESCC	2.56e-52	1.13e+00	0.171
3191	HNRNPL	P126T-E	Human	Esophagus	ESCC	3.76e-15	1.50e+00	0.1125
3191	HNRNPL	P127T-E	Human	Esophagus	ESCC	8.80e-57	1.06e+00	0.0826
3191	HNRNPL	P128T-E	Human	Esophagus	ESCC	2.60e-59	2.08e+00	0.1241
3191	HNRNPL	P130T-E	Human	Esophagus	ESCC	1.24e-102	2.08e+00	0.1676
3191	HNRNPL	NAFLD1	Human	Liver	NAFLD	8.27e-04	3.69e-01	-0.04
3191	HNRNPL	S43	Human	Liver	Cirrhotic	9.38e-08	-1.32e-01	-0.0187
3191	HNRNPL	HCC1_Meng	Human	Liver	HCC	7.17e-62	-5.12e-02	0.0246
3191	HNRNPL	HCC2_Meng	Human	Liver	HCC	1.10e-26	1.08e-01	0.0107
3191	HNRNPL	cirrhotic3	Human	Liver	Cirrhotic	4.20e-09	2.02e-01	0.0215
3191	HNRNPL	HCC1	Human	Liver	HCC	1.24e-07	3.22e+00	0.5336
3191	HNRNPL	HCC2	Human	Liver	HCC	8.01e-14	2.47e+00	0.5341
3191	HNRNPL	Pt13.a	Human	Liver	HCC	4.77e-05	-2.15e-01	0.021
3191	HNRNPL	Pt14.a	Human	Liver	HCC	3.13e-03	1.98e-01	0.0169
3191	HNRNPL	S014	Human	Liver	HCC	1.36e-28	1.07e+00	0.2254
3191	HNRNPL	S015	Human	Liver	HCC	1.00e-12	8.63e-01	0.2375
3191	HNRNPL	S016	Human	Liver	HCC	4.37e-18	8.47e-01	0.2243
3191	HNRNPL	S027	Human	Liver	HCC	2.45e-09	1.15e+00	0.2446
3191	HNRNPL	S028	Human	Liver	HCC	8.92e-18	1.11e+00	0.2503
3191	HNRNPL	S029	Human	Liver	HCC	6.84e-24	1.22e+00	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0000377	Colorectum	AD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000398	Colorectum	AD	mRNA splicing, via spliceosome	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000375	Colorectum	AD	RNA splicing, via transesterification reactions	131/3918	324/18723	7.11e-16	2.22e-13	131
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0043484	Colorectum	AD	regulation of RNA splicing	70/3918	148/18723	6.47e-13	1.16e-10	70
GO:0048024	Colorectum	AD	regulation of mRNA splicing, via spliceosome	50/3918	101/18723	1.62e-10	1.56e-08	50
GO:0050684	Colorectum	AD	regulation of mRNA processing	61/3918	137/18723	4.23e-10	3.58e-08	61
GO:0000380	Colorectum	AD	alternative mRNA splicing, via spliceosome	33/3918	77/18723	1.13e-05	2.55e-04	33
GO:0000381	Colorectum	AD	regulation of alternative mRNA splicing, via spliceosome	27/3918	60/18723	2.41e-05	4.66e-04	27
GO:00083801	Colorectum	SER	RNA splicing	123/2897	434/18723	3.84e-12	8.41e-10	123
GO:00003751	Colorectum	SER	RNA splicing, via transesterification reactions	90/2897	324/18723	8.68e-09	7.50e-07	90
GO:00003771	Colorectum	SER	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00003981	Colorectum	SER	mRNA splicing, via spliceosome	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00434841	Colorectum	SER	regulation of RNA splicing	49/2897	148/18723	7.02e-08	4.49e-06	49
GO:19033111	Colorectum	SER	regulation of mRNA metabolic process	78/2897	288/18723	2.61e-07	1.43e-05	78
GO:00480241	Colorectum	SER	regulation of mRNA splicing, via spliceosome	35/2897	101/18723	1.52e-06	6.85e-05	35
GO:00506841	Colorectum	SER	regulation of mRNA processing	42/2897	137/18723	5.57e-06	2.01e-04	42
GO:00003801	Colorectum	SER	alternative mRNA splicing, via spliceosome	24/2897	77/18723	4.08e-04	6.09e-03	24
GO:00003811	Colorectum	SER	regulation of alternative mRNA splicing, via spliceosome	20/2897	60/18723	4.60e-04	6.65e-03	20

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

HNRNPL

SNV

Missense_Mutation

c.1540N>A

p.Glu514Lys

p.E514K

P14866

protein_coding

deleterious(0.03)

benign(0.033)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HNRNPL

SNV

Missense_Mutation

novel

c.502N>A

p.Pro168Thr

p.P168T

P14866

protein_coding

deleterious(0.04)

probably_damaging(0.999)

TCGA-A7-A3RF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

HNRNPL

SNV

Missense_Mutation

c.1391N>T

p.Ser464Leu

p.S464L

P14866

protein_coding

tolerated(0.51)

benign(0.059)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HNRNPL

SNV

Missense_Mutation

novel

c.1560N>G

p.Ile520Met

p.I520M

P14866

protein_coding

tolerated(0.23)

benign(0.001)

TCGA-AC-A3W5-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

HNRNPL

insertion

Frame_Shift_Ins

novel

c.850_851insCCTTAGAAACCAGCAGTGGCTCCTTTGAGAGTCTGGTGAGGGT

p.Asp284AlafsTer26

p.D284Afs*26

P14866

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

HNRNPL

insertion

Frame_Shift_Ins

novel

c.1284_1285insAG

p.Gly429ArgfsTer5

p.G429Rfs*5

P14866

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HNRNPL

insertion

In_Frame_Ins

novel

c.1283_1284insGGGCCCAATTTCACAAGAACCGCATTGGCG

p.Asp428delinsGluGlyProIleSerGlnGluProHisTrpArg

p.D428delinsEGPISQEPHWR

P14866

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HNRNPL

SNV

Missense_Mutation

c.1021N>A

p.Glu341Lys

p.E341K

P14866

protein_coding

tolerated(0.56)

benign(0.018)

TCGA-C5-A1MI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HNRNPL

SNV

Missense_Mutation

c.719N>T

p.Ser240Leu

p.S240L

P14866

protein_coding

tolerated(0.09)

benign(0.057)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HNRNPL

SNV

Missense_Mutation

c.796N>A

p.Glu266Lys

p.E266K

P14866

protein_coding

deleterious(0.02)

benign(0.017)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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